tbuckley/cabot-search huggingface dataset:
Radiation Facility Volume and Survival for Men With Very High-Risk Prostate Cancer Treated with Radiation and Androgen Deprivation Therapy
Authors: Nikhil Sebastian, Subir Goyal, Yuan Liu, James R. Janopaul-Naylor, Pretesh R. Patel, Vishal R. Dhere, Sheela Hanasoge, Jay W. Shelton, Karen D. Godette, Ashesh B. Jani, Bruce Hershatter, Benjamin Fischer-Valuck, Sagar A. Patel
Journal: JAMA Network Open (2023)

Importance Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment—resources more readily available at high-volume centers. Objective To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. Design, Setting, and Participants A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, &amp;amp;gt;4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Exposures Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient’s treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Main Outcomes and Measures Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. Results A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers ( P &amp;amp;lt; .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P &amp;amp;lt; .001). These results were also significant after inverse probability score weighted–based adjustment. Conclusions and Relevance In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.
Enhancing Lactation Accommodations for Physicians—An Opportunity for Tangible Investments in Our Workforce
Authors: Lisa S. Rotenstein, Marcela G. del Carmen, Jessica Dudley
Journal: JAMA Network Open (2023)

Despite evidence of their delivering better outcomes of care, 1 women physicians continue to face numerous challenges in the workforce.These range from lower average compensation to differences in promotion and experiences of harassment, ultimately resulting in higher rates of burnout 2 and a greater likelihood of reducing their clinical effort. 3These challenges are amplified in the postpartum period, when, in addition to the demands of caring for a new child, women physicians struggle to find time and space for lactation and may lose compensation in systems where their pay is based on clinical productivity.
Timing of lifespan influences on brain and cognition
Authors: Kristine B. Walhovd, Martin Lövden, Anders M. Fjell
Journal: Trends in Cognitive Sciences (2023)

Modifiable risk and protective factors for boosting brain and cognitive development and preventing neurodegeneration and cognitive decline are embraced in neuroimaging studies. We call for sobriety regarding the timing and quantity of such influences on brain and cognition. Individual differences in the level of brain and cognition, many of which present already at birth and early in development, appear stable, larger, and more pervasive than differences in change across the lifespan. Incorporating early-life factors, including genetics, and investigating both level and change will reduce the risk of ascribing undue importance and causality to proximate factors in adulthood and older age. This has implications for both mechanistic understanding and prevention.
H3K4 trimethylation regulates cancer immunity: a promising therapeutic target in combination with immunotherapy
Authors: Chu Xiao, Tao Fan, Yujia Zheng, He Tian, Ziqin Deng, Jingjing Liu, Chunxiang Li, Jie He
Journal: Journal for ImmunoTherapy of Cancer (2023)

With the advances in cancer immunity regulation and immunotherapy, the effects of histone modifications on establishing antitumor immunological ability are constantly being uncovered. Developing combination therapies involving epigenetic drugs (epi-drugs) and immune checkpoint blockades or chimeric antigen receptor-T cell therapies are promising to improve the benefits of immunotherapy. Histone H3 lysine 4 trimethylation (H3K4me3) is a pivotal epigenetic modification in cancer immunity regulation, deeply involved in modulating tumor immunogenicity, reshaping tumor immune microenvironment, and regulating immune cell functions. However, how to integrate these theoretical foundations to create novel H3K4 trimethylation-based therapeutic strategies and optimize available therapies remains uncertain. In this review, we delineate the mechanisms by which H3K4me3 and its modifiers regulate antitumor immunity, and explore the therapeutic potential of the H3K4me3-related agents combined with immunotherapies. Understanding the role of H3K4me3 in cancer immunity will be instrumental in developing novel epigenetic therapies and advancing immunotherapy-based combination regimens.
A common thalamic hub for general and defensive arousal control
Authors: Yiwei Wang, Ling You, KaMun Tan, Meijie Li, Jingshan Zou, Zhifeng Zhao, Wenxin Hu, Tianyu Li, Fenghua Xie, Caiqin Li, Ruizhi Yuan, Kai Ding, Lingwei Cao, Fengyuan Xin, Congping Shang, Miaomiao Liu, Yixiao Gao, Liqiang Wei, Zhiwei You, Xiaorong Gao, Wei Xiong, Peng Cao, Minmin Luo, Feng Chen, Kun Li, Jiamin Wu, Bo Hong, Kexin Yuan
Journal: Neuron (2023)
The Antimicrobial, Hemostatic, and Anti‐Adhesion Effects of a Peptide Hydrogel Constructed by the All‐<scp>d</scp>‐Enantiomer of Antimicrobial Peptide Jelleine‐1
Authors: Hanru Zhang, Zhiyu Wu, Jingjing Zhou, Zhaopeng Wang, Changyan Yang, Panpan Wang, Muhammad Subaan Fareed, Yuhang He, Jie Su, Ruitao Cha, Kairong Wang
Journal: Advanced Healthcare Materials (2023)

Peptide hydrogels are believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and 3D printability. Most of the previously reported polypeptide hydrogels are composed of l-peptides, while the hydrogels formed by self-assembly of d-peptides are rarely reported. Herein, a peptide hydrogel constructed by D-J-1, which is the all-d-enantiomer of antimicrobial peptide Jelleine-1 (J-1) is reported. Field emission scanning electron microscope (FE-SEM) and rheologic study are performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti-adhesion studies are carried out to evaluate its biofunction. The results show that D-J-1 hydrogel is formed by self-assembly and cross-linking driven by hydrogen bonding, hydrophobic interaction, and π–π stacking force of aromatic ring in the structure of D-J-1. It exhibits promising antimicrobial activity, hemostatic activity, and anti-adhesion efficiency in a rat sidewall defect-cecum abrasion model. In addition, it also exhibits good biocompatibility. Notably, D-J-1 hydrogel shows improved in vitro and in vivo stability when compared with its l-enantiomer J-1 hydrogel. Therefore, the present study will provide new insight into the application of d-peptide hydrogel, and provides a new peptide hydrogel with antibacterial, hemostatic, and anti-adhesion efficacy for clinical use.
Pregnancy‐related thromboembolism in women with sickle cell disease: An analysis of <scp>National Medicaid Data</scp>
Authors: Shreya Agarwal, Joseph R. Stanek, Sara K. Vesely, Susan E. Creary, Robert M. Cronin, Andrea H. Roe, Sarah H. O'Brien
Journal: American Journal of Hematology (2023)

Pregnancy and sickle cell disease (SCD) both individually carry a risk of thromboembolism (TE). Pregnancy in people with SCD may further enhance the prothrombotic effect of the underlying disease. The objectives of this study were to determine the rate and risk factors for arterial and venous thrombosis in pregnant people with SCD. Administrative claims data from the United States Centers for Medicare and Medicaid Service Analytic eXtract from 2006 to 2018 were used. The study population included people with SCD from the start of their first identified pregnancy until 1 year postpartum and a control cohort of pregnant people without SCD of similar age and race. Outcomes of interest were identified with ICD-9 or 10 codes. Logistic regression analyses were used to analyze risk factors. We identified infant deliveries in 6388 unique people with SCD and 17 110 controls. A total of 720 venous thromboembolism (11.3%) and 335 arterial TE (5.2%) were observed in people with SCD compared to 202 (1.2%) and 95 (0.6%) in controls. People with SCD had an 8-11 times higher odds of TE compared to controls (p < .001). Within the SCD cohort, age, hemoglobin SS (HbSS) genotype, hypertension, and history of thrombosis were identified as independent risk factors for pregnancy-related TE. Pregnancy-specific factors (pre-eclampsia, eclampsia, multigestational pregnancy) were not associated with TE. In conclusion, the risk of pregnancy-related TE is considerably higher in people with SCD compared with controls without SCD. Hence, people with SCD, particularly those with multiple risk factors may be candidates for thromboprophylaxis during pregnancy and the postpartum period.
Organ Donation After Out-of-Hospital Cardiac Arrest: A Scientific Statement From the International Liaison Committee on Resuscitation
Authors: Laurie J. Morrison, Claudio Sandroni, Brian Grunau, Michael Parr, Finlay Macneil, Gavin D. Perkins, Mayuki Aibiki, Eileen Censullo, Steve Lin, Robert W. Neumar, Steven C. Brooks
Journal: Circulation (2023)

AIM OF THE REVIEW: Improving rates of organ donation among patients with out-of-hospital cardiac arrest who do not survive is an opportunity to save countless lives. The objectives of this scientific statement were to do the following: define the opportunity for organ donation among patients with out-of-hospital cardiac arrest; identify challenges and opportunities associated with organ donation by patients with cardiac arrest; identify strategies, including a generic protocol for organ donation after cardiac arrest, to increase the rate and consistency of organ donation from this population; and provide rationale for including organ donation as a key clinical outcome for all future cardiac arrest clinical trials and registries. METHODS: The scope of this International Liaison Committee on Resuscitation scientific statement was approved by the International Liaison Committee on Resuscitation board and the American Heart Association, posted on ILCOR.org for public comment, and then assigned by section to primary and secondary authors. A unique literature search was completed and updated for each section. RESULTS: There are a number of defining pathways for patients with out-of-hospital cardiac arrest to become organ donors; however, modifications in the Maastricht classification system need to be made to correctly identify these donors and to report outcomes with consistency. Suggested modifications to the minimum data set for reporting cardiac arrests will increase reporting of organ donation as an important resuscitation outcome. There are a number of challenges with implementing uncontrolled donation after cardiac death protocols, and the greatest impediment is the lack of legislation in most countries to mandate organ donation as the default option. Extracorporeal cardiopulmonary resuscitation has the potential to increase organ donation rates, but more research is needed to derive neuroprognostication rules to guide clinical decision-making about when to stop extracorporeal cardiopulmonary resuscitation and to evaluate cost-effectiveness. CONCLUSIONS: All health systems should develop, implement, and evaluate protocols designed to optimize organ donation opportunities for patients who have an out-of-hospital cardiac arrest and failed attempts at resuscitation.
Specific detection of tau seeding activity in Alzheimer’s disease using rationally designed biosensor cells
Authors: Aurelien Lathuiliere, Youhwa Jo, Romain Perbet, Cameron Donahue, Caitlin Commins, Noé Quittot, Zhanyun Fan, Rachel E Bennett, Bradley T Hyman
Journal: Molecular Neurodegeneration (2023)

Abstract Background The prion-like propagation of tau in neurodegenerative disorders implies that misfolded pathological tau can recruit the normal protein and template its aggregation. Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity. Results We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer’s disease. We generated Förster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer’s disease. Conclusions This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer’s disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.
Eosinophilic allergic rhinitis is strongly associated with the <scp>CD45RB<sup>lo</sup></scp> subset of <scp>CD161</scp><sup>+</sup> Th2 cells that secretes <scp>IL</scp>‐2, <scp>IL</scp>‐3, <scp>IL</scp>‐4, <scp>IL</scp>‐5, <scp>IL</scp>‐9, and <scp>IL</scp>‐13
Authors: Wendy W. L. Lee, Kia Joo Puan, Bernett Lee, Celine Chua, Ser Mei Koh, Nurhashikin Yusof, Kim Peng Tan, Boris San Luis, Jocelyn Ong, Simon Kebede Merid, Rachel Ang, Xue Ying Chan, Low Jing Hui, Elisa Terenzani, Josephine Lum, Shihui Foo, Francesca Zolezzi, Annabelle Tay Sok Yan, Erik Melen, Soh Jian Yi, Olaf Rotzschke, Anand Kumar Andiappan
Journal: Allergy (2023)

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Table S1. Figure S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Association between baseline lactate dehydrogenase and immune-related adverse events among patients with melanoma varies by tumor stage at immune checkpoint inhibitor initiation
Authors: Catherina X. Pan, William C. Lau, Daniel Y. Kim, Charles B. Lau, Rachael Rowley, Ruhi Kanwar, Nicole R. LeBoeuf, Vinod E. Nambudiri
Journal: Journal of the American Academy of Dermatology (2023)
New immunotherapy strategies for patients with sarcomas: highlights from the 2023 ASCO annual meeting
Authors: Matthieu Roulleaux-Dugage, Antoine Italiano
Journal: Journal of Hematology & Oncology (2023)

Abstract Immunotherapy has revolutionized cancer treatment, but currently, immuno-oncology agents have not been approved for patients with soft tissue sarcomas. However, there is growing evidence suggesting that immunotherapy could be an effective therapeutic strategy for this group of diseases. Here, we reviewed the latest advances of immunotherapy trials from the 2023 American Society of Clinical Oncology Annual Meeting, including some novel and encouraging combination regimens. Further research is still needed to fully understand the optimal use of these agents in sarcoma treatment.
Robust cross-cohort gut microbiome associations with COVID-19 severity
Authors: Junhui Li, Tarini Shankar Ghosh, Rachel MacCann, Patrick Mallon, Colin Hill, Lorraine Draper, David Schult, Liam J. Fanning, Robert Shannon, Corinna Sadlier, Mary Horgan, Liam O’Mahony, Paul W. O’Toole
Journal: Gut Microbes (2023)

Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7–30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with Actinomyces oris abundance predicting population-level mortality rate of COVID-19. Additionally, we used relational diet-microbiome databases constructed from cohort studies to predict microbiota-targeted diet patterns that would modulate gut microbiota composition toward that of healthy controls. Finally, we demonstrated the association of disease severity with the composition of intestinal archaeal, fungal, viral, and parasitic communities. Collectively, this study has identified robust COVID-19 microbiome biomarkers, established accurate predictive models as a basis for clinical prognostic tests for disease severity, and proposed biomarker-targeted diets for managing COVID-19 infection.
Complement C1q essential for aeroallergen sensitization via CSF1R+ conventional dendritic cells type 2
Authors: Hyung-Geun Moon, Jacob D. Eccles, Seung-jae Kim, Ki-Hyun Kim, Young-Mee Kim, Jalees Rehman, Hyun Lee, Pinal Kanabar, John W. Christman, Steven J. Ackerman, Christian Ascoli, Homan Kang, Hak Soo Choi, Minhyung Kim, Sungyong You, Gye Young Park
Journal: Journal of Allergy and Clinical Immunology (2023)
Lipid‐based nanoparticles as drug delivery systems for cancer immunotherapy
Authors: Yang Hao, Zhonghao Ji, Hengzong Zhou, Dongrun Wu, Zili Gu, Dongxu Wang, Peter ten Dijke
Journal: MedComm (2023)

Abstract Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation‐related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type‐specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno‐oncology therapy with a focus on lipid‐based NPs (lipid‐NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid‐NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid‐NPs to enhance cancer immunotherapy.
The acute effects of repetitive transcranial magnetic stimulation on laminar diffusion anisotropy of neocortical gray matter
Authors: Wenjing Zhang, Naici Liu, Youjin Zhao, Chenyang Yao, Dan Yang, Chengmin Yang, Hui Sun, Xia Wei, John A. Sweeney, Huilou Liang, Miaoqi Zhang, Qiyong Gong, Su Lui
Journal: MedComm (2023)

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to treat neuropsychiatric disorders. Inhibitory and excitatory regimens have been both adopted but the exact mechanism of action remains unclear, and investigating their differential effects on laminar diffusion profiles of neocortex may add important evidence. Twenty healthy participants were randomly assigned to receive a low-frequency/inhibitory or high-frequency/excitatory rTMS targeting the left dorsolateral prefrontal cortex (DLPFC). With the brand-new submillimeter diffusion tensor imaging of whole brain and specialized surface-based laminar analysis, fractional anisotropy (FA) and mean diffusion (MD) profiles of cortical layers at different cortical depths were characterized before/after rTMS. Inhibitory and excitatory rTMS both showed impacts on diffusion metrics of somatosensory, limbic, and sensory regions, but different patterns of changes were observed-increased FA with inhibitory rTMS, whereas decreased FA with excitatory rTMS. More importantly, laminar analysis indicated laminar specificity of changes in somatosensory regions during different rTMS patterns-inhibitory rTMS affected the superficial layers contralateral to the DLPFC, while excitatory rTMS led to changes in the intermediate/deep layers bilateral to the DLPFC. These findings provide novel insights into acute neurobiological effects on diffusion profiles of rTMS that may add critical evidence relevant to different protocols of rTMS on neocortex.
Erratum to “Aligning tumor mutational burden (TMB) quantification across diagnostic platforms: phase II of the Friends of Cancer Research TMB Harmonization Project”
Authors: D.M. Vega, L.M. Yee, L.M. McShane, P.M. Williams, L. Chen, T. Vilimas, D. Fabrizio, V. Funari, J. Newberg, L.K. Bruce, S.-J. Chen, J. Baden, J. Carl Barrett, P. Beer, M. Butler, J.-H. Cheng, J. Conroy, D. Cyanam, K. Eyring, E. Garcia, G. Green, V.R. Gregersen, M.D. Hellmann, L.A. Keefer, L. Lasiter, A.J. Lazar, M.-C. Li, L.E. MacConaill, K. Meier, H. Mellert, S. Pabla, A. Pallavajjalla, G. Pestano, R. Salgado, R. Samara, E.S. Sokol, P. Stafford, J. Budczies, A. Stenzinger, W. Tom, K.C. Valkenburg, X.Z. Wang, V. Weigman, M. Xie, Q. Xie, A. Zehir, C. Zhao, Y. Zhao, M.D. Stewart, J. Allen
Journal: Annals of Oncology (2023)